Method of stabilizing aqueous pyrazoloacridone derivative solution

Abstract

An aqueous solution of a pyrazoloacridone compound or pharmaceutical salt is stabilized using an acid, placing the solution in a well-closed container, evacuating air in the container, and sealing the container.

What is claimed is:  
     
       1. A method for stabilizing an aqueous solution containing a pyrazoloacridone compound or a pharmaceutically acceptable salt thereof, comprising: 
       adding an acid to a container of an aqueous solution comprising a pyrazoloacridone compound represented by formula (I):                    
        wherein R 1a , R 1b , R 1c  and R 1d  independently represent hydrogen, a lower alkyl group, —(CH 2 ) p —X (wherein p is an integer of 1 to 6; and X represents a hydroxyl group, a lower alkoxy group, or —NR 2a R 2b  (wherein R 2a  and R 2b  independently represent hydrogen, a lower alkyl group, —(CH 2 ) m —Y (wherein m is an integer of 1 to 6; and Y represents a hydroxyl group, a lower alkoxy group, or —NR 3a R 3b  (wherein R 3a  and R 3b  independently represent hydrogen or a lower alkyl group)), or R 2a  and R 2b  form a heterocyclic group together with the nitrogen atom adjacent thereto)), or —CH((CH 2 ) n OH) 2  (wherein n is an integer of 1 to 5) or a pharmaceutically acceptable salt thereof;  
       evacuating air from the container; and  
       sealing the container.  
     
     
       2. The method as claimed in  claim 1 , wherein the acid is an organic acid represented by the following formula (II): 
       
         
           R 4 R 5 CH—COOH  (II)  
         
       
       wherein R 4  represents hydrogen or hydroxy; and R 5  represents hydrogen, carboxy, or alkyl having from 1 to 3 carbon atoms which may be substituted with hydroxy or carboxy. 
     
     
       3. The method as claimed in  claim 1 , wherein the acid is lactic acid. 
     
     
       4. The method as claimed in any of  claims 1  to  3 , wherein the aqueous solution has a pH of 2 to 6. 
     
     
       5. A well-closed container comprising an aqueous solution containing a pyrazoloacridone compound represented by formula (I):                    
       wherein R 1a , R 1b , R 1c  and R 1d  independently represent hydrogen, a lower alkyl group, —(CH 2 ) p —X (wherein p is an integer of 1 to 6; and X represents a hydroxyl group, a lower alkoxy group, or —NR 2a R 2b  (wherein R 2a  and R 2b  independently represent hydrogen, a lower alkyl group, —(CH 2 ) m —Y (wherein m is an integer of 1 to 6; and Y represents a hydroxyl group, a lower alkoxy group, or —NR 3a R 3b  (wherein R 3a  and R 3b  independently represent hydrogen or a lower alkyl group)), or R 2a  and R 2b  form a heterocyclic group together with the nitrogen atom adjacent thereto)), or —CH((CH 2 ) n OH) 2  (wherein n is an integer of 1 to 5), or a pharmaceutically acceptable salt thereof, and an acid, 
       wherein an atmosphere in the well-closed container does not contain air.  
     
     
       6. The well-closed container as claimed in  claim 5  wherein said acid is an organic acid represented by the following formula (II): 
       
         
           R 4 R 5 CH—COOH  (II)  
         
       
       wherein R 4  represents hydrogen or hydroxy; and R 5  represents hydrogen, carboxy, or alkyl having from 1 to 3 carbon atoms which may be substituted with hydroxy or carboxy. 
     
     
       7. The well-closed container as claimed in  claim 5 , wherein the acid is lactic acid. 
     
     
       8. The well known container as claimed in any of  claims 5  to  7 , wherein the aqueous solution has a pH of 2 to 6. 
     
     
       9. The method as claimed in any of  claims 1  to  3 , wherein the evacuated container is filled with an inert gas. 
     
     
       10. The method as claimed in  claim 9 , wherein the inert gas is nitrogen gas. 
     
     
       11. The method as claimed in  claim 4 , wherein the evacuated container is filled with an inert gas. 
     
     
       12. The well-closed container as claimed in any of claims  5 - 7 , wherein the atmosphere inside the container is inert. 
     
     
       13. The well-closed container as claimed in  claim 8 , wherein the atmosphere inside the container is inert. 
     
     
       14. The well-closed container as claimed in  claim 12 , wherein the inert gas is nitrogen gas. 
     
     
       15. The well-closed container as claimed in  claim 13 , wherein the inert gas is nitrogen gas. 
     
     
       16. The method as claimed in  claim 11 , wherein the inert gas is nitrogen gas.